Approach towards an operational tool to apply institutional analysis for the assessment of policy feasibility within SEAMLESS-IF

Environmental Economics and Policy,

Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis is associated with level and avidity of anti-cyclic citrullinated protein autoantibodies: a case study

In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity

Economic valuation of water services related to protected forest management: a case of Bukit Batabuh in the RIMBA corridor, Central Sumatra, Indonesia

The context of daily household needs of rural communities, particularly the needs for water, often remains insufficiently considered in tropical forest management as it is facing an important decision-making trade-off between profit and preservation. We conducted a choice experiment study to elicit preferences of the rural community members in Central Sumatra, Indonesia, who perpetually depend on the ecosystem services of tropical forests. To inform a spatial planning policy for the protected forest, we focus on the valuation of water services in the protected forest area of Bukit Batabuh where the surrounding communities living rely on upstream watershed and water storage management. We find that those communities have a strict preference for improving forest water provisioning services, compared to the current situation (status quo), with the estimated aggregate benefit of non-commercial use ranging between USD 2.71 million and USD 2.47 million per year for each of the options of (1) maintaining and enhancing water storage, (2) rehabilitating forest in the upper watershed or (3) restoring the riparian forest. This study also identifies preference attributes, such as water storage capacity, water scarcity and water turbidity which can be used in other tropical landscape contexts in Indonesia and beyond

Fatty acid synthase overexpression: target for therapy and reversal of chemoresistance in ovarian cancer

BACKGROUND: Fatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells’ increased demands for membrane, energy, and protein production. METHODS: We investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. FASN inhibition’s impact on cell viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection enzyme-linked immunosorbent assay, immunoblotting, and (18) F-fluoromethylcholine uptake measurement, respectively. RESULTS: Relative to that in healthy fallopian tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell lines and primary cultures had 11-fold–100-fold mRNA and protein overexpression. In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression and cell viability and induced apoptosis. Unlike concomitant administration, sequential cerulenin/cisplatin treatment reduced cisplatin’s half maximal inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed lower (18) F-fluoro-methylcholine uptake than did cisplatin-sensitive cells, suggesting that metabolic imaging might help guide therapy. CONCLUSIONS: FASN inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian cancer cells and may reverse cisplatin resistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0511-3) contains supplementary material, which is available to authorized users

A Delphi study to guide the development of a clinical indicator tool for Palliative Care in South Africa

BACKGROUND: The South African National Policy Framework and Strategy on Palliative Care (NPFSPC) recommends that when integrating palliative care (PC) into the health system, a PC indicators tool should be used to guide clinicians to recognise a patient who should receive PC. The policy document recommends ‘a simple screening tool developed for use in South Africa that would assist healthcare professionals (HCPs) to recognise patients who may have unmet palliative care needs’. AIM: This research study sought to develop South African consensus on indicators for PC to assist clinicians to recognise a patient in need of PC. SETTING: The South African healthcare setting. METHODS: A Delphi study was considered suitable as a methodology to develop consensus. The methodology was based on the Conducting and REporting of DElphi studies (CREDES) guidance on Delphi studies to ensure rigour and transparency in conducting and reporting. Six different Delphi rounds were used to develop consensus. Each round allowed participants to anonymously rate statements with predefined rating scales. RESULTS: Cognisant of the disparities in healthcare provision and access to equitable healthcare in South Africa, the expert advisory group recommended, especially for South Africa, that ‘this tool is for deteriorating patients with an advanced life-limiting illness where all available and appropriate management for underlying illnesses and reversible complications has been offered’. The expert advisory group felt that disease-specific indicators should be described before the general indicators in the South African indicators tool, so all users of the tool orientate themselves to the disease categories first. This study included three new domains to address the South African context: trauma, infectious diseases and haematological diseases. General indicators for PC aligned with the original Supportive and Palliative Care Indicators Tool (SPICT) tool. CONCLUSION: The Supportive and Palliative Care Indicators Tool for South Africa (SPICT(TM)-SA) is a simple screening tool for South Africa that may assist HCPs to recognise patients who may have unmet PC needs

Economic valuation of water services related to protected forest management: a case of Bukit Batabuh in the RIMBA corridor, Central Sumatra, Indonesia

The context of daily household needs of rural communities, particularly the needs for water, often remains insufficiently considered in tropical forest management as it is facing an important decision-making trade-off between profit and preservation. We conducted a choice experiment study to elicit preferences of the rural community members in Central Sumatra, Indonesia, who perpetually depend on the ecosystem services of tropical forests. To inform a spatial planning policy for the protected forest, we focus on the valuation of water services in the protected forest area of Bukit Batabuh where the surrounding communities living rely on upstream watershed and water storage management. We find that those communities have a strict preference for improving forest water provisioning services, compared to the current situation (status quo), with the estimated aggregate benefit of non-commercial use ranging between USD 2.71 million and USD 2.47 million per year for each of the options of (1) maintaining and enhancing water storage, (2) rehabilitating forest in the upper watershed or (3) restoring the riparian forest. This study also identifies preference attributes, such as water storage capacity, water scarcity and water turbidity which can be used in other tropical landscape contexts in Indonesia and beyond